This proposal is formulated to study the effect of Rhodamine B dye laser irradiation (635 nm) on hematoporphyrin derivative (HPD) (absorbance spectrum 600-700 nm) sensitized and nonsensitized human bladder tumor cells. The specific aims are: (1) to determine the photocytotoxicity of cultured human bladder tumor cells and normal human fibroblasts exposed to laser irradiation with and without prior photosensitization by HPD; (2) to attempt to modify a known murine bladder tumor model such that human bladder tumor cells may be implanted into the denuded bladder epithelium of athymic nude mice; (3) to use this murine model to study the ability of laser irradiation to selectively destroy implanted human bladder tumors with and without prior selective photosensitization by various dosages of HPD administered by either intravenous, intraperitoneal, or intravesical routes; and (4) to determine the short and long term effects of laser irradiation both on HPD sensitized and nonsensitized implanted human bladder tumors and on adjacent normal mouse bladder epithelium. This study combines the clinical disciplines of urology and the clinically seldom utilized biomedical laboratory discipline of laser technology. Laser energy has been shown to be efficiently transmitted over fiberoptics so that diffuse endoscopic laser irradiation of photosensitized bladder tumors in humans might offer a new dimension in their treatment. This treatment may be more effective in destroying not only invasive bladder tumors which heretofore have demanded treatment associated with significant morbidity and mortality, preinvasive malignant conditions such as carcinoma in situ which is often multifocal, and also difficult to recognize premalignant (dysplastic) conditions as well. Therefore, laser treatment of photosensitized bladder tumors may be equal to or more effective and associated with less morbidity than current conventional treatment. Should laser treatment of hematoporphyrin derivative sensitized human bladder tumors in mice prove efficacious, then subsequent research will be directed towards determining the best routes of administration and dosage of hematoporphyrin derivative in humans to allow maximal tumor uptake, minimal uptake by normal tissues, and minimal systemic toxicity.